Radiation Therapy Combined With Chemotherapy in Treating Patients With Anaplastic Astrocytoma or Mixed Gliomas
- Conditions
- Brain and Central Nervous System Tumors
- Interventions
- Registration Number
- NCT00004259
- Lead Sponsor
- Radiation Therapy Oncology Group
- Brief Summary
RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. Drugs used in chemotherapy, such as temozolomide, carmustine, and lomustine, use different ways to stop tumor cells from dividing so they stop growing or die. Combining radiation therapy with chemotherapy may kill more tumor cells.
PURPOSE: This randomized phase III trial is studying radiation therapy and temozolomide to see how well they work compared to radiation therapy and carmustine or lomustine in treating patients with anaplastic astrocytoma or mixed gliomas.
- Detailed Description
OBJECTIVES:
* Compare the overall survival and time to tumor progression in patients with anaplastic astrocytoma or mixed gliomas treated with radiotherapy combined with temozolomide vs carmustine or lomustine vs temozolomide and carmustine (arm discontinued as of 8/15/02).
* Compare the relative toxic effects of these regimens in these patients.
* Correlate molecular analyses with overall survival and time to tumor progression in patients treated with these regimens.
OUTLINE: This is a randomized, multicenter study. Patients are stratified according to age (under 50 vs 50 and over), Karnofsky performance status (60-80% vs 90-100%), and prior surgery (biopsy only vs resection).
Phase I
* Pilot Arms I and II: Prior to initiating the randomization to 1 of 3 treatment arms in phase III, Patients are accrued to Arm III regimen to determine tolerability.
Phase III
* Patients are randomized to 1 of 2 treatment arms (3rd arm was dropped).
* Arm I: Patients undergo radiotherapy 5 days a week for 6 weeks. Patients receive oral temozolomide on days 1-5 of the first week of radiotherapy. Chemotherapy repeats every 4 weeks for a total of 12 courses.
* Arm II: Patients undergo radiotherapy as in arm I. Patients receive carmustine IV or lomustine IV over 1-2 hours on days 1-3 of the first week of radiotherapy and a second course on days 56-58. Chemotherapy repeats every 8 weeks for a total of 6 courses.
* Arm III (dropped, did not open): Patients undergo radiotherapy as in arm I. Patients receive carmustine IV or lomustine IV over 3 hours on day 5 and oral temozolomide (2 hours after completion of carmustine or lomustine infusion) on days 1-5 of the first week of radiotherapy. Combination chemotherapy repeats every 8 weeks for 6 courses.
Patients are followed every 3 months for 1 year, every 6 months for 2 years, and then annually thereafter.
PROJECTED ACCRUAL: Phase I: 30 patients; Phase III: 454 patients (227 per treatment arm) within 4 years.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 230
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Pilot Arm #2: RT+TMZ+BCNU TMZ 150mg/m2 six 8-week cycles Radiation therapy for 6 weeks concurrent with and followed by BCNU 150mg/m2 and TMZ 150mg/m2 six 8-week cycles Radiation therapy + temozolomide (TMZ) TMZ 200mg/m2 Radiation therapy (RT) for 6 weeks concurrent with and followed by TMZ 200mg/m2 for twelve 28-day cycles Pilot Arm #1: RT+TMZ+BCNU BCNU 200mg/m2 Radiation therapy for 6 weeks concurrent with and followed by BCNU 200mg/m2 and TMZ 150mg/m2 six 6-week cycles Pilot Arm #1: RT+TMZ+BCNU TMZ 150mg/m2 six 6-week cycles Radiation therapy for 6 weeks concurrent with and followed by BCNU 200mg/m2 and TMZ 150mg/m2 six 6-week cycles RT + BCNU/CCNU CCNU Radiation therapy for 6 weeks concurrent with and followed by BCNU 80mg/m2 or CCNU 130 mg/m2 for six 8-week cycles RT + BCNU/CCNU BCNU 80mg/m2 Radiation therapy for 6 weeks concurrent with and followed by BCNU 80mg/m2 or CCNU 130 mg/m2 for six 8-week cycles Pilot Arm #1: RT+TMZ+BCNU radiation therapy Radiation therapy for 6 weeks concurrent with and followed by BCNU 200mg/m2 and TMZ 150mg/m2 six 6-week cycles Pilot Arm #2: RT+TMZ+BCNU radiation therapy Radiation therapy for 6 weeks concurrent with and followed by BCNU 150mg/m2 and TMZ 150mg/m2 six 8-week cycles RT + BCNU/CCNU radiation therapy Radiation therapy for 6 weeks concurrent with and followed by BCNU 80mg/m2 or CCNU 130 mg/m2 for six 8-week cycles Radiation therapy + temozolomide (TMZ) radiation therapy Radiation therapy (RT) for 6 weeks concurrent with and followed by TMZ 200mg/m2 for twelve 28-day cycles Pilot Arm #2: RT+TMZ+BCNU BCNU 150mg/m2 Radiation therapy for 6 weeks concurrent with and followed by BCNU 150mg/m2 and TMZ 150mg/m2 six 8-week cycles
- Primary Outcome Measures
Name Time Method (Phase III) Overall Survival (OS) From randomization to date of death. Patients are followed until death. Analysis occurs after 155 deaths have been reported, estimated at 5.5 years from the study opening. Survival time is defined as time from randomization to date of death from any cause and is estimated by the Kaplan-Meier method. Patients last known to be alive are censored at the date of last contact. Per the protocol, the pilot arms were not included in the Phase III analyses.
(Phase I) Number of Subjects With Dose Limiting Toxicities (DLT) on the Two Pilot Arms From start of treatment to 3 months Adverse events were graded using CTCAE v2.0. Grade refers to the severity of the adverse event (AE). The CTCAE v2.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild AE, Grade 2 Moderate AE, Grade 3 Severe AE, Grade 4 Life-threatening or disabling AE, Grade 5 Death related to AE. Dose limiting toxicity (DLT) was defined as grade 3+ pulmonary toxicity, grade 4+ thrombocytopenia (\< 25,000 for 5 days), neutropenia (\< 500/microl for 7 days), or neutropenia of any duration with fever requiring hospital admission after one dose reduction of 50% in BCNU. A 20% rate of grade 3+ pulmonary toxicities or a 40% rate of grade 4+ thrombocytopenia and neutropenia was considered unacceptable for a treatment arm combining RT, TMZ, and BCNU.
- Secondary Outcome Measures
Name Time Method (Phase III) Time to Tumor Progression (TTP) From randomization to date of death. Patients are followed until death. Analysis occurs after 155 deaths have been reported, estimated at 5.5 years from the study opening. Three-year rate is reported. Progression is defined as a radiographic increase in size of the lesion by \> 25%, recurrence of the study lesion, or the development of new lesions, confirmed by imaging. Time to tumor progression was estimated using the cumulative incidence function (CIF) on tumor progression, with death as a competing risk. Per the protocol, the pilot arms were not included in the Phase III analyses.
(Phase III) Number of Patients With Grade 3 or Higher Toxicity From randomization to date of death. Patients are followed until death. Analysis occurs after 155 deaths have been reported, estimated at 5.5 years from the study opening. Adverse events were graded using CTCAE v2.0. Grade refers to the severity of the AE. The CTCAE v2.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild AE, Grade 2 Moderate AE, Grade 3 Severe AE, Grade 4 Life-threatening or disabling AE, Grade 5 Death related to AE. The number of patients with grade or higher toxicity was calculated overall and for non-hematologic toxicity only. Per the protocol, the pilot arms were not included in the Phase III analyses.
(Phase III) Survival Time by MGMT Status From randomization to date of death. Patients are followed until death. Analysis occurs after 155 deaths have been reported, estimated at 5.5 years from the study opening. Survival time is defined as time from randomization to date of death from any cause and is estimated by the Kaplan-Meier method. Patients last known to be alive are censored at the date of last contact. Tumor tissue samples were analyzed for methylation status of methyl guanine methyl transferase (MGMT), classified as methylated vs. unmethylated.
(Phase III) Progression-free Survival by MGMT Status From randomization to date of death. Patients are followed until death. Analysis occurs after 155 deaths have been reported, estimated at 5.5 years from the study opening. Progression is defined as a radiographic increase in size of the lesion by \> 25%, recurrence of the study lesion, or the development of new lesions, confirmed by imaging. Progression-free survival time is defined as time from randomization to date of progression or death from any cause and is estimated by the Kaplan-Meier method. Patients last known to be alive are censored at the date of last contact. Tumor tissue samples were analyzed for methylation status of methyl guanine methyl transferase (MGMT), classified as methylated vs. unmethylated.
Trial Locations
- Locations (92)
Fox Chase Virtua Health Cancer Program at Virtua Memorial Hospital Marlton
🇺🇸Marlton, New Jersey, United States
Fox Chase Virtua Health Cancer Program at Virtua West Jersey
🇺🇸Voorhees, New Jersey, United States
Mason District Hospital
🇺🇸Havana, Illinois, United States
Greenebaum Cancer Center at University of Maryland Medical Center
🇺🇸Baltimore, Maryland, United States
University of Wisconcin Cancer Center at Aspirus Wausau Hospital
🇺🇸Wausau, Wisconsin, United States
University Medical Center of Southern Nevada
🇺🇸Las Vegas, Nevada, United States
CCOP - Nevada Cancer Research Foundation
🇺🇸Las Vegas, Nevada, United States
Charles M. Barrett Cancer Center at University Hospital
🇺🇸Cincinnati, Ohio, United States
North Bay Cancer Center
🇺🇸Fairfield, California, United States
Mobile Infirmary Medical Center
🇺🇸Mobile, Alabama, United States
Solano Radiation Oncology Center
🇺🇸Vacaville, California, United States
Lynn Regional Cancer Center at Boca Raton Community Hospital - Main Center
🇺🇸Boca Raton, Florida, United States
Enloe Cancer Center at Enloe Medical Center
🇺🇸Chico, California, United States
Florida Oncology Associates at Southside Cancer Center
🇺🇸Jacksonville, Florida, United States
Integrated Community Oncology Network
🇺🇸Jacksonville Beach, Florida, United States
Baptist Cancer Institute - Jacksonville
🇺🇸Jacksonville, Florida, United States
Florida Oncology Associates
🇺🇸Orange Park, Florida, United States
Florida Cancer Center - Palatka
🇺🇸Palatka, Florida, United States
Baptist Medical Center South
🇺🇸Jacksonville, Florida, United States
Flagler Cancer Center
🇺🇸Saint Augustine, Florida, United States
John B. Amos Cancer Center
🇺🇸Columbus, Georgia, United States
St. Joseph Medical Center
🇺🇸Bloomington, Illinois, United States
Memorial Hospital
🇺🇸Carthage, Illinois, United States
Graham Hospital
🇺🇸Canton, Illinois, United States
Eureka Community Hospital
🇺🇸Eureka, Illinois, United States
InterCommunity Cancer Center of Western Illinois
🇺🇸Galesburg, Illinois, United States
Galesburg Clinic
🇺🇸Galesburg, Illinois, United States
Galesburg Cottage Hospital
🇺🇸Galesburg, Illinois, United States
McDonough District Hospital
🇺🇸Macomb, Illinois, United States
Hopedale Medical Complex
🇺🇸Hopedale, Illinois, United States
BroMenn Regional Medical Center
🇺🇸Normal, Illinois, United States
Oncology Hematology Associates of Central Illinois, PC - Ottawa
🇺🇸Ottawa, Illinois, United States
Community Cancer Center
🇺🇸Normal, Illinois, United States
Community Hospital of Ottawa
🇺🇸Ottawa, Illinois, United States
Proctor Hospital
🇺🇸Peoria, Illinois, United States
Cancer Treatment Center at Pekin Hospital
🇺🇸Pekin, Illinois, United States
OSF St. Francis Medical Center
🇺🇸Peoria, Illinois, United States
CCOP - Illinois Oncology Research Association
🇺🇸Peoria, Illinois, United States
Methodist Medical Center of Illinois
🇺🇸Peoria, Illinois, United States
Illinois Valley Community Hospital
🇺🇸Peru, Illinois, United States
Perry Memorial Hospital
🇺🇸Princeton, Illinois, United States
St. Margaret's Hospital
🇺🇸Spring Valley, Illinois, United States
Cancer Center of Kansas, PA - Kingman
🇺🇸Kingman, Kansas, United States
CCOP - Montana Cancer Consortium
🇺🇸Billings, Montana, United States
CCOP - Duluth
🇺🇸Duluth, Minnesota, United States
St. John's Regional Health Center
🇺🇸Springfield, Missouri, United States
West Michigan Cancer Center
🇺🇸Kalamazoo, Michigan, United States
Deaconess Billings Clinic - Downtown
🇺🇸Billings, Montana, United States
Good Samaritan Cancer Center at Good Samaritan Hospital
🇺🇸Kearney, Nebraska, United States
Franklin & Edith Scarpa Regional Cancer Center at South Jersey Healthcare
🇺🇸Vineland, New Jersey, United States
Mission Hospitals - Memorial Campus
🇺🇸Asheville, North Carolina, United States
Akron City Hospital
🇺🇸Akron, Ohio, United States
Case Comprehensive Cancer Center
🇺🇸Cleveland, Ohio, United States
Natalie Warren Bryant Cancer Center at St. Francis Hospital
🇺🇸Tulsa, Oklahoma, United States
Cancer Research UK Medical Oncology Unit at Churchill Hospital & Weatherall Institute of Molecular Medicine - Oxford
🇺🇸Salem, Ohio, United States
Allegheny Cancer Center at Allegheny General Hospital
🇺🇸Pittsburgh, Pennsylvania, United States
Kimmel Cancer Center at Thomas Jefferson University - Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
Guthrie Cancer Center at Guthrie Clinic Sayre
🇺🇸Sayre, Pennsylvania, United States
Theda Care Cancer Institute
🇺🇸Appleton, Wisconsin, United States
Rapid City Regional Hospital
🇺🇸Rapid City, South Dakota, United States
Reading Hospital and Medical Center
🇺🇸Reading, Pennsylvania, United States
St. Vincent Hospital Regional Cancer Center
🇺🇸Green Bay, Wisconsin, United States
Bay Area Cancer Care Center at Bay Area Medical Center
🇺🇸Marinette, Wisconsin, United States
Community Memorial Hospital Cancer Care Center
🇺🇸Menomonee Falls, Wisconsin, United States
Cancer Center of Kansas, PA - Dodge City
🇺🇸Dodge City, Kansas, United States
Cancer Center of Kansas, PA - El Dorado
🇺🇸El Dorado, Kansas, United States
Cancer Center of Kansas, PA - Newton
🇺🇸Newton, Kansas, United States
Cancer Center of Kansas, PA - Parsons
🇺🇸Parsons, Kansas, United States
Cotton-O'Neil Cancer Center
🇺🇸Topeka, Kansas, United States
Cancer Center of Kansas, PA - Chanute
🇺🇸Chanute, Kansas, United States
Southwest Medical Center
🇺🇸Liberal, Kansas, United States
Cancer Center of Kansas, PA - Salina
🇺🇸Salina, Kansas, United States
Cancer Center of Kansas, PA - Wellington
🇺🇸Wellington, Kansas, United States
Cancer Center of Kansas, PA - Pratt
🇺🇸Pratt, Kansas, United States
Cancer Center of Kansas, PA - Winfield
🇺🇸Winfield, Kansas, United States
Arizona Oncology Services Foundation
🇺🇸Phoenix, Arizona, United States
Latter Day Saints Hospital
🇺🇸Salt Lake City, Utah, United States
Kewanee Hospital
🇺🇸Kewanee, Illinois, United States
Valley Cancer Center
🇺🇸Spring Valley, Illinois, United States
H. Lee Moffitt Cancer Center and Research Institute at University of South Florida
🇺🇸Tampa, Florida, United States
Methodist Cancer Center at Methodist Hospital - Omaha
🇺🇸Omaha, Nebraska, United States
Cancer Center of Kansas, PA - Wichita
🇺🇸Wichita, Kansas, United States
University of Florida Shands Cancer Center
🇺🇸Gainesville, Florida, United States
Associates in Womens Health, PA - North Review
🇺🇸Wichita, Kansas, United States
Cancer Center of Kansas, PA - Medical Arts Tower
🇺🇸Wichita, Kansas, United States
CCOP - Wichita
🇺🇸Wichita, Kansas, United States
Via Christi Cancer Center at Via Christi Regional Medical Center
🇺🇸Wichita, Kansas, United States
Wesley Medical Center
🇺🇸Wichita, Kansas, United States
Lipson Cancer and Blood Center at Rochester General Hospital
🇺🇸Rochester, New York, United States
Oncology Hematology Associates of Central Illinois, PC - Peoria
🇺🇸Peoria, Illinois, United States
McFarland Clinic, PC
🇺🇸Ames, Iowa, United States
Cancer Treatment Center
🇺🇸Wooster, Ohio, United States